The D&T Report

In the quest to balance the growing demand for kidneys with a perennially scarce donor supply, some intrepid transplant surgeons are taking another look at individuals the Centers for Disease Control and Prevention (CDC) label “highrisk,” such as sex workers, men who have sex with men, injection drug users, and people with acute kidney injuries. Many transplant centerswould summarily reject organs from these people, due largely to the risk of HIV transmission.

But desperate times call for desperate measures, says Dorry Segev, MD, PhD, associate professor of surgery and epidemiology and director of clinical research at Johns Hopkins Department of Surgery in Baltimore. “There are 90,000 people on the waiting list, and the death rate while on the waiting list is quite high,” says Dr. Segev. “Some people have a greater than 50% chance of dying before they receive their first organ offer.”He believes the donor pool could be expanded considerably if transplant centers increase their willingness to consider “high-risk” organs. “These are still functioning kidneys, and if there are people for whom [the risk of contracting HIV] is lower than the risk of dying while on dialysis, it might be worth it tomake that decision.”

All in all, approximately 10% of donors fall into the high-risk category, says Niraj Desai, MD, surgical director of kidney transplantation at the Johns Hopkins Comprehensive Transplant Center. “Over the last year or two, we've probably done about 100 transplants of organs from donors who have engaged in CDC high-risk behaviors, and we have not had any donor-derived transmission of HIV or hepatitis C.”

People who have suffered an acute kidney injury requiring temporary dialysis represent another potential group of donors who might ordinarily be rejected bymany centers. Usually, these kidneys come from young donors who do not have any kidney pathology, except this acute injury. These are known as high-terminal creatinine kidneys, inwhich the high creatinine levels are associated with the donor's death, not any intrinsic problem with the kidney. “These kidneys do well if you put them in someone who can tolerate the delay in return to graft function, and whose cardiac function can support the allograft through the phase of initial ischemia. Eventually, those organs can turn around,” adds Dr. Desai.

“We have used many kidneys where the terminal creatininewas as high as 4, 5, and even 8 mg/dL,” says Dr. Desai. If the donors are relatively young (usually 40 years old or younger), and if a biopsy can document a lack of chronic changes, the organs may be suitable for some recipients. Acute tubular necrosis is usually the main pathologic finding, but “we don't want to see a lot of scarring in the interstitium, glomerular sclerosis, or arterial vessel thickening, which would indicate that there has been long-term vessel damage, which may impede the kidney's ability to recover from the acute insult,” he adds.

The injuries sustained by these kidneys are not always trivial. “As the desperation of the patients on the list grows higher, the list grows longer, and organ availability is not getting any better, we've had to stretch the envelope even further,” says Dr. Desai. “So now we are considering using organs that have taken such a hit that the donors have ended up on temporary hemodialysis.”One example, he says, is a donor who has sustained a major anoxic injury leading to brain death.When the kidneys shut down as they sometimes do in these patients, the ICU staff, along with the organ procurement organization, may initiate temporary dialysis and remove fluid from the patient to enhance cardiac and pulmonary function and optimize placement of all the organs.

Many centers hesitate to use kidneys from such donors but, says Dr. Desai, “for us, it's just further out on the spectrum of acute kidney injury. The word dialysis doesn't scare us away if the other criteria are met.” The key is to use continuous venovenous hemodiafiltration (CVVHDF), which permits the slow and steady removal of fluid that prevents dramatic swings in blood pressure, permits gradual clearance of solutes and toxins, and helps prevent metabolic problems such as acid-base imbalance or hyperkalemia. CVVHDF may also be used on living ICU patients, including potential donors who have extreme kidney injuries that may be reversible, saysDr. Desai.

What types of patients would be offered such a kidney? “An older recipient who doesn't have a long time to wait on the list because of their age, or whowould not do well on dialysis for a long period of time; these patients might be good candidates if they can tolerate the operation and the period of delayed graft function that usually follows.” The kidneys almost always function well eventually, he points out.

Sometimes it is not the donor who is considered high risk, but the recipient. Morbid obesity, for example, is traditionally considered an unacceptable risk factor for renal transplantation, says Enrico Benedetti, MD, professor and head of the department of surgery, University of Illinois at Chicago (UIC). About 60% of transplant centers in the U.S. place an upper limit on body mass index (BMI) of 35, and only a handful accept patients with a BMI >40, Dr. Benedetti tells “The D&T Report.” Yet many obese patients are diabetic, and diabetic patients have a dismal record of survival on dialysis: about 22% at five years.

Obese patients often are considered poor candidates for organ transplantation because of their high risk of perioperative wound infection: as much as 15% to 25% in people with a BMI of 40, compared with less than 5% in non-obese patients, says Dr. Benedetti, who also co-directs the university's transplant center. “We thought we could manipulate this particular risk factor. Instead of making a large incision in the lower abdomen,we perform the entire transplant using a small, 7-cm incision in the upper abdomen, which is just large enough to place the kidney in the abdominal cavity. The dissection of the vessels and the vascular suturing is done with the robot.”

So far, Dr. Benedetti and his colleagues have operated on 25 patients, the heaviest with a BMI of 58, and only one has developed a superficial wound infection. That translates into an infection rate of 4%, similar to what is seen in non-obese patients. “To date, all of the kidneys have worked immediately, and all but one have come from living donors,” says Dr. Benedetti. The patients all undergo the standard selection processwhen being considered for transplant, and they do not turn down any patient simply because of their body weight. Potential contraindications include significant peripheral vascular disease, particularly disease in the iliac vessels, and patients older than 50 years of age undergo a special cardiovascular workup.

So far, the government has paid for these procedures. “Medicare doesn't care if you do the transplant with the robot or with your bare hands,” notesDr. Benedetti. “The fee is exactly the same, so there is no added cost to the patient.” Other payers may require more persuasion. The UIC team is planning a meeting with a large private insurer to demonstrate that, since obese patients currently are less likely to undergo transplantation, they spend more time on dialysis, which is farmore expensive than a transplant (which becomes cost-effective within 16 months). The medication regimen and other aspects of postsurgical care are exactly the same as they are for conventional patients.

Currently, UIC is the only center performing these transplants on obese individuals, but several other centers have expressed interest, “and of course we will be happy to train anyone who wants to come and learn,” says Dr. Benedetti.

The courage and creativity that gave us organ transplantation to begin with is now finding ways of increasing the organ supply. That supply is still too small, but these innovative approaches offer hope to patients of the future.

The previous edition of The D&T Report looked at some of the moral and ethical arguments made for and against organ donation by prisoners.1 Some ethicists believe that prisoners cannot really make an unfettered decision precisely because they are imprisoned, while others see nothing wrong with it, as long as there is no evidence of direct coercion. Besides, why not give convicted criminals the chance to redeem themselves by doing something good for society?

There is, of course, no right or wrong answer, and the ethical debate will undoubtedly continue for as long as the organ shortage persists. The perspective shifts, however, when the question focuses on prisoners sentenced to death. Many opponents point to China: Not only is it the only country in the world where organ harvesting from executed prisoners is legal; there is good evidence that many prisoners– often those who disagree with the government's policies–are killed specifically for that reason.

But some people on death row in the U.S. want to be deceased organ donors, and appear to have arrived at this decision completely voluntarily, despite the ethical concerns described above. One case in point is Christian Longo, a condemned prisoner in Oregon who published an article in the New York Times arguing that he should be allowed to donate his organs after his execution.2 The state has consistently denied his requests.

Why shouldn't Longo, and others like him, be permitted to donate their organs upon their execution, as long as it can be demonstrated that they are doing so of their own free will? Because it would place organ-procurement teams at an ugly interface between ethics and clinical reality. “There is no interest in the transplant community to use prisoners as a source of organs,” says Francis Delmonico,MD, professor of surgery at Harvard University in Boston. When asked if this might not be a way for prisoners to atone for their crimes, he says, “Not if it requires someone else to procure your organs as the basis for your atonement.”

Even the most willing death-row donor might not be medically suitable. “People on death row usually are older, because they've been through a lot of appeals, they're usually in poor shape because they've been eating bad food and don't exercise much, and they have a high risk of infectious disease,” says Arthur Caplan, PhD, professor of bioethics and philosophy at the University of Pennsylvania in Philadelphia.

The logistics of organ removal and preservation also are daunting. “There certainly would be damage tomost organs thatwould occur if the person's heartwas not beating for a prolonged period of time prior to organ removal,” says Niraj Desai, MD, surgical director of kidney transplantation at the Johns Hopkins Comprehensive Transplant Center in Baltimore. “It would be challenging to come up with a scenario in which you could be sure that the person is no longer alive, yet preserve the organs well enough to be useable.”

What this means is that even before the execution, physicians would have to become involved in the process by evaluating the prisoner to determine if he or she would be a suitable donor. And they would have to be present at the time of death, if not actually be the agents of death, in order to begin resuscitation and organ retrieval. 3 Dr. Delmonico's retort encapsulates the medical community's objection to death-row organ donation: As explained in a white paper by the OPTN/UNOS Ethics Committee, anesthetizing the prisoner, cross-clamping the aorta, performing a cardiectomy, and disconnecting the ventilator “clearly places the organ recovery team in the role of executioner.”4 This is the slippery ethical slope thatmost transplant clinicians fear.

The 9th Annual Kidney Times Essay Contest, sponsored byRenal Support Network (RSN), is now accepting entries. All people who have been diagnosed with chronic kidney disease and who love to write are encouraged to enter. This year's theme is: “What hobby helps improve your quality of life and helps you forget the many challenges kidney disease presents?”

There are cash prizes of $500, $300, and $100 for the top three entries and an additional $100 cash prize for the best Spanish essay. All winnerswill be featured on the front page of the Kidney Times website and featured in RSN's publication Live & Give.

Entries must be received by August 1, 2011. Prospective entrants can visit www.kidneytimes.com or www.rsnhope.org formore information and contest rules.

In an effort to estimate the prevalence of chronic kidney disease (CKD) in adults with type 2 diabetes and examine the care of these individuals, the National Kidney Foundation (NKF) is launching a multi-site cross-sectional study, “Awareness, Detection and Drug Therapy in Type 2 Diabetes Mellitus and Chronic Kidney Disease” (ADD-CKD), to assess how CKDis being identified and managed in type 2 diabetic patients in the primary care setting.

Researchers will recruit 460 primary care practitioner providers for the study. Each provider will recruit 21 type 2 diabetes patients, for a total of 9,660 patients. The study, to be administered by primary care physicians and primary care nurse practitioners, will use a primary care provider survey, a patient physical exam and medical history, lab testing (including blood and urine analysis), and patient quality-of-life questionnaires.

Study enrollment begins this month. Primary care providers can fill out an online feasibility survey available at www.kidney.org.

Adecreasing number ofU.S. medical students are adopting nephrology as a career, according to a review appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology(CJASN).

The review, by Mark G. Parker, MD, American Society of Nephrology (ASN) Workforce Committee chair and nephrologist atMaine Medical Center in Portland, and colleagues, highlights the declining interest of medical students in the U.S. in nephrology. Although talented internationalmedical graduates have historically contributed substantially to the U.S. nephrology workforce, it is increasingly difficult for international medical graduates to obtain visas for the U.S. and this compounds the problem created by decreasing U.S. medical student interest in nephrology.

The ASN has started to implement strategies to inspire interest in nephrology among U.S. medical graduates by helping to provide stimulating experiences for trainees, nurture outstanding educators, and use social media to encourage the next generation of students to learn about the importance of kidney disease and the satisfaction many nephrologists derive from improving kidney care. The organization will also step up efforts to recruit women and minorities-both currently underrepresented in the nephrology physicianworkforce. While gains were made by females, Hispanics, andAfricanAmericans entering nephrology fellowships from 2002 to 2009, these increases still trailed gains made by other medical subspecialties.

Nephros, a medical device company that develops and markets filtration products for therapeutic applications, infection control, and water purification, has received approval from the Therapeutic Products Directorate of Health Canada, the Canadian health regulatory agency, to market its dual stage ultrafilters in Canada to filter biological contaminants from water and bicarbonate solution used in hemodialysis procedures.

In the U.S., the Dual StageUltrafilters are FDA-cleared as devices for the filtration of biological contaminants from water and bicarbonate concentrate used in hemodialysis procedures. The filter can be used as the last step in the water purification process to ensure that ultrapure water is used for dialysis procedures.

NxStage Medical has received regulatory approval from Australia's TherapeuticGoodsAdministration (TGA) for the NxStage System One home dialysis machine and signed a five-year agreement, the first year ofwhich is exclusive, with Regional Health Care Group (RHCG), a medical products distributer in Australia and New Zealand.

Under the terms of the agreement with RHCG, the NxStage System One and PureFlow dialysate preparation system will be available to dialysis centers throughout Australia and New Zealand through RHCG. RHCG also has the option to make Medisystems bloodlines and ButtonHole needles available to their customers in the region.